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OIT and Xolair® (Omalizumab) in Cow's Milk Allergy

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Hugh A Sampson, MD, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT01157117
First received: July 2, 2010
Last updated: March 8, 2016
Last verified: March 2016
Results First Received: January 5, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Milk Allergy
Interventions: Biological: Placebo for omalizumab
Biological: Omalizumab
Drug: Milk powder

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Omalizumab/Milk OIT Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.
Placebo for Omalizumab/Milk OIT Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC; if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.
Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.

Participant Flow:   Overall Study
    Omalizumab/Milk OIT     Placebo for Omalizumab/Milk OIT     Untreated Control  
STARTED     28     29     20  
Began Omalizumab or Placebo Dosing     27     28     0  
Began Milk OIT Dosing at Month 4     27     28     0  
Reached Milk OIT Maintenance Dosing     26     26     0  
Unblinded at Month 16     26     26     0  
Completed Month 28 Desensitization OFC     26     24     0  
Discontinued Milk OIT at Month 30     24     20     0  
Completed Month 32 Tolerance OFC     24     20     0  
Completed Final Month 38 Study Visit     19     18     3  
COMPLETED     19 [1]   18 [1]   5 [1]
NOT COMPLETED     9     11     15  
Dosing Symptoms                 0                 4                 0  
Withdrawal by Subject                 4                 1                 1  
Lack of Efficacy                 1                 1                 0  
Lost to Follow-up                 0                 0                 1  
Unknown (Pending Final Form Submission)                 4                 5                 13  
[1] Completed final study visit at Month 38, 6 months after final Month 32 OFC.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Omalizumab/Milk OIT Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization OFC. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28 participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.
Placebo for Omalizumab/Milk OIT Placebo for omalizumab: Placebo for omalizumab is injected subcutaneously every 2-4 weeks for 16 months at a volume designed to match that of the omalizumab treatment group (determined by the participant's immunoglobulin E (IgE) level and weight).
Untreated Control Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.
Total Total of all reporting groups

Baseline Measures
    Omalizumab/Milk OIT     Placebo for Omalizumab/Milk OIT     Untreated Control     Total  
Number of Participants  
[units: participants]
  28     29     20     77  
Age  
[units: participants]
       
<=18 years     26     27     20     73  
Between 18 and 65 years     2     2     0     4  
>=65 years     0     0     0     0  
Gender  
[units: participants]
       
Female     8     9     5     22  
Male     20     20     15     55  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic or Latino origin     0     2     0     2  
Non-Hispanic or non-Latino origin     28     27     20     75  
Race/Ethnicity, Customized  
[units: participants]
       
Asian     4     3     2     9  
Black/African American     1     0     0     1  
White     23     26     18     67  
Region of Enrollment  
[units: participants]
       
United States     28     29     20     77  
Age  
[units: years]
Mean (Standard Deviation)
  12.6  (4.1)     11.5  (5.6)     11.3  (2.9)     11.8  (4.5)  
Atopic Dermatitis Total Score [1]
[units: Scores on a scale]
Mean (Standard Deviation)
  0.3  (0.9)     0.5  (1.5)     1.0  (2.3)     0.5  (1.5)  
Total IgE [2]
[units: kU/L]
Mean (Standard Deviation)
  683.1  (658.9)     686.6  (565.7)     878.8  (824.3)     735.2  (670.3)  
Milk IgE [3]
[units: kUA/L]
Mean (Standard Deviation)
  52.2  (47.4)     57.9  (55.5)     72.4  (63.9)     59.6  (54.9)  
Milk Skin Prick Test Score [4]
[units: mm]
Mean (Standard Deviation)
  8.9  (3.3)     9.0  (3.2)     NA [5]   8.9  (3.2)  
Age at Initial Milk Allergic Reaction [6]
[units: years]
Mean (Standard Deviation)
  0.9  (1.8)     0.5  (0.5)     0.9  (0.8)     0.7  (1.1)  
[1] The Atopic Dermatitis Total Score is scored on a 10 point scale of 0 to 9 where a higher score indicates increasing severity of atopic dermatitis. This score is a combination of three scores that range from 0 to 3 in the following areas: body surface area score, disease course, and disease intensity. Note: These data were only available for 12 of the 20 Untreated Control participants.
[2] Total amount of serum immunoglobulin E (IgE).
[3] Amount of serum milk-specific immunoglobulin E (IgE). Individuals with a milk IgE of <0.35 kUA/L (allergen-equivalent kilounits per liter) are considered not to be sensitized to milk.
[4] This score is calculated by subtracting the size of the saline wheal (in mm) from the size of the milk wheal (in mm) observed for a skin prick test. Individuals with a milk skin prick test score of < 3 mm are considered to have a negative result.
[5] Data were not collected for this group.
[6] Age in years at the participant's first milk allergic reaction. Note: These data were only available for 14 of the 28 Omalizumab/Milk OIT participants, 19 of the 29 Placebo for Omalizumab/Milk OIT participants, and 14 of the 20 Untreated Control participants.



  Outcome Measures
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1.  Primary:   Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk   [ Time Frame: Month 32 which is 8 weeks following the discontinuation of milk OIT for both groups and 4 months after discontinuation of omalizumab for the omalizumab group ]

2.  Secondary:   Incidence of Dosing Reactions to Milk OIT During the Escalation Phase   [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]

3.  Secondary:   Incidence of Dosing Reactions to Milk OIT During the Maintenance Phase   [ Time Frame: After completion of Escalation Phase at 22 to 40 weeks, the Maintenance Phase lasted up to Month 30 ]

4.  Secondary:   Incidence of Severe Hypersensitivity Reactions to Milk OIT   [ Time Frame: Through completion of milk OIT dosing (at Month 28 if failed desensitization OFC, at Month 30 if passed desensitization OFC) ]

5.  Secondary:   Maximum Tolerated Dose of Milk Oral Immunotherapy (OIT)   [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]

6.  Secondary:   Percentage of Participants in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Desensitization to Milk   [ Time Frame: Month 28 ]

7.  Secondary:   Change in Endpoint Milk Skin Prick Test Titration and Mechanistic Assays to Evaluate Biologic Responses   [ Time Frame: Month 32 & Month 38 ]

8.  Secondary:   Time to Maximum Tolerated Dose   [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Hugh A. Sampson
Organization: Ichan School of Medicine at Mount Sinai
phone: 212-659-9426
e-mail: hugh.sampson@mssm.edu


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hugh A Sampson, MD, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01157117     History of Changes
Other Study ID Numbers: DAIT AADCRC-MSSM-01
U19AI044236 ( US NIH Grant/Contract Award Number )
Study First Received: July 2, 2010
Results First Received: January 5, 2016
Last Updated: March 8, 2016
Health Authority: United States: Food and Drug Administration